Uric acid has a J-shaped association with cardiovascular and all-cause mortality in kidney transplant recipients.

The association between serum uric acid and kidney graft and recipient survival is uncertain. During 2000-2011, we measured serum uric acid at week 10 after transplantation. Of 2748 transplanted patients, 2200 (80.1%) attended this visit. After a median follow-up of 7.4 yr, 378 patients had died, 143 from a cardiovascular cause, and 185 patients lost their graft. The third quintile of uric acid levels (357-405 µM) had the lowest mortality risk and was used as reference group. In Cox proportional hazard models adjusting for graft and patient characteristics, the fifth quintile of uric acid levels (>474 µM) was independently associated with cardiovascular mortality (hazard ratio [HR] = 2.87 [1.55-5.32], p = 0.001) and all-cause mortality (HR = 1.57 [1.09-2.25], p = 0.02). Also, the lowest quintile of uric acid levels (<309 µM) showed a trend toward increased risk of cardiovascular mortality (HR = 1.79 [0.90-3.58], p = 0.10) and all-cause mortality (HR = 1.31 [0.89-1.93], p = 0.18). The increased risk at low uric acid levels was confined to diabetic recipients. Uric acid was not associated with death-censored graft loss. In conclusion, uric acid has a J-shaped association with cardiovascular and all-cause mortality in kidney transplant recipients.

MC1R, ASIP, TYR, and TYRP1 gene variants in a population-based series of multiple primary melanomas.

Allelic variants of the low-penetrance melanoma gene MC1R increase the risk of both melanoma and non-melanoma skin cancer. Common variants of the genes ASIP, TYR, and TYRP1, which regulate the melanogenic pathway, have also been shown to associate with melanoma. In this population-based study, we investigated SNPs of MC1R, ASIP, TYR, and TYRP1 as risk factors for development of multiple primary melanomas (MPM) in 388 Norwegian cases. The MPM patients had a significantly higher likelihood of carrying any MC1R variant than the control group of 420 blood donors [86.8 vs. 78.3%, OR = 1.73, and confidence intervals (CI) 1.18-2.52]. When MC1R variants were analyzed individually, Asp84Glu and Arg151Cys were significantly more frequent among the MPM cases than among the controls (OR = 5.77, CI 1.97-16.90, and OR = 1.80, CI 1.36-2.37, respectively). In addition, there was an allele dose-dependent increase in MPM risk for carriers of red hair color (RHC) MC1R variants. The AH haplotype of ASIP was also a significant risk factor for MPM development (OR = 1.72 and CI 1.12-2.49), whereas no association was observed for previously reported risk variants of the TYR and TYRP1 genes. In summary, by using a population-based material of high-risk melanoma cases, we demonstrate a significant effect of both MC1R RHC variants and an ASIP haplotype, but could not replicate an association with postulated risk SNPs of TYR and TYRP1.

Acute renal failure early after heart transplantation: risk factors and clinical consequences.

Limited information exists about acute renal failure (ARF) early after heart transplantation (HTx). We correlated pre-, per-, and post-operative patient and donor parameters to the risk of developing ARF. We also analyzed the consequences of ARF on kidney function after HTx, risk of later need for chronic dialysis or kidney transplantation, and mortality. In a retrospective study from 1983 to 2007, 145 (25%) of 585 HTx recipients developed ARF, defined as ≥ 26.4 micromol/L or ≥ 50% increase in serum creatinine from pre-operatively to the seventh day post-HTx and/or the need of early post-operative dialysis. Independent risk factors for ARF were intravenous cyclosporine immediately post-operatively (odds ratio [OR] 2.16, 95% CI 1.34-3.50, p = 0.02), donor age (OR 1.02, 95% CI 1.00-1.04, p = 0.02), and pre-operative cardiac output (OR 1.38, 95% CI 1.12-1.71, p = 0.003). The development of ARF was a predictor for short-term survival (≤ 3 months) ranging from 98% for patients who improved their creatinine after HTx vs. 79% for those in need of dialysis (p < 0.001). However, ARF did not predict subsequent end stage renal disease in need of dialysis or renal transplantation. ARF is a common complication post-HTx. As ARF is associated with short-term survival, post-operative strategies of preserving renal function have the potential of reducing mortality. Of avoidable risk factors, the use of intravenous CsA should be discouraged.

Variability in patch test reactions--first report from the Norwegian Patch Test Registry.

BACKGROUND: A nation-wide Norwegian Patch Test Registry (NOLAR) was established in 2005 as a collaboration between six dermatology departments. International, multi-centre studies have documented great variability in the frequency of positive patch test reactions, considered as mainly due to heterogeneity of test populations. OBJECTIVES: To analyse the variability of positive test reactions by studying patch tests performed at the six collaborating departments, using standardized procedures. MATERIALS AND METHODS: Data from all patch tests (n = 2089) performed in 2007-2008 as registered in the NOLAR program. Differences between centres were analysed using Exact Pearson chi(2) test. RESULTS: Between the centres, positive test reactions (+, ++, or +++) varied significantly for 8 of the 26 allergens in the European Baseline Series. When considering strong reactions (++ or +++) only, the differences were statistically significant for six of these allergens, i.e. cobalt chloride, potassium dichromate, p-phenylenediamine, formaldehyde, paraben mix, and mercaptobenzothiazole. CONCLUSION: The results indicate regional differences in the prevalence of sensitization to certain allergens within the Norwegian population, although inter-observer differences cannot be ruled out as a factor.

Development and Validation of the CPO Scale, a New Instrument for Evaluation of Health Care Improvement Efforts.

OBJECTIVE: To develop and validate an instrument for guidance and evaluation of quality and safety improvement efforts in health care. CONTEXT: The instrument is based on the Plan-Do-Study-Act cycle and the 3 fundamental improvement questions regarding aims, measurement, and change-making. METHODS: An interdisciplinary team of improvement experts developed the Change Process and Outcome (CPO) scale. After studying the improvement literature, the scale was tested and refined on a sample of 5 projects. The CPO evaluation process and classification system was developed when evaluating 189 of the quality improvement projects of the Norwegian Medical Association by their final reports. The scale was validated by applying statistical testing to the evaluation results. RESULTS: The final CPO scale consists of 13 process items and 7 outcome items. Interrater reliability ranged from 0.53 to 0.79, and test-retest reliability was 0.82. Factor analyses with Varimax rotation identified 2 significant process domains: Aims/change-making and Measurement/reporting, with Cronbach α values 0.88 and 0.95, respectively. The classification system produced 3 performance levels: successful, promising, and uncertain. CONCLUSION: The CPO scale shows good internal consistency, reliability, and validity for evaluating the success of quality improvement initiatives.

Ethnic differences in neonatal body composition in a multi-ethnic population and the impact of parental factors: a population-based cohort study.

BACKGROUND: Neonates from low and middle income countries (LAMIC) tend to have lower birth weight compared with Western European (WE) neonates. Parental height, BMI and maternal parity, age and educational level often differ according to ethnic background, and are associated with offspring birth weight. Less is known about how these factors affect ethnic differences in neonatal body composition. OBJECTIVES: To explore differences in neonatal body composition in a multi-ethnic population, and the impact of key parental factors on these differences. METHODS: A population-based cohort study of pregnant mothers, fathers and their offspring, living in Oslo, Norway. Gender- and gestational-specific z-scores were calculated for several anthropometric measurements, with the neonates of WE ethnic origin as reference. Mean z-scores for neonates with LAMIC origin, and their parents, are presented as outcome variables. RESULTS: 537 singleton, term neonates and their parents were included. All anthropometric measurements were smaller in neonates with LAMIC origin. Abdominal circumference and ponderal index differed the most from WE (mean z-score: -0.57 (95% CI:-0.69 to -0.44) and -0.54 (-0.66 to -0.44), and remained so after adjusting for parental size. Head circumference and skin folds differed less, and length the least (-0.21 (-0.35 to -0.07)). These measures became comparable to WEs when adjusted for parental factors. CONCLUSIONS: LAMIC origin neonates were relatively "thin-fat", as indicated by reduced AC and ponderal index and relatively preserved length and skin folds, compared with neonates with WE origin. This phenotype may predispose to type 2 diabetes.

Epidemiological aspects of recurrent respiratory papillomatosis: a population-based study.

OBJECTIVES/HYPOTHESIS: The incidence of genital infections, cervical cancer, and oropharyngeal cancer induced by human papillomaviruses (HPV) is increasing in Western countries. Primarily, this study was conducted to estimate the incidence rate of recurrent respiratory papillomatosis (RRP) in juveniles and adults in two Norwegian subpopulations for each year between 1987 and 2009. The secondary objective of the study was to investigate whether there are trends in the incidence rates of RRP in the study period similar to what we have seen for HPV-related cancer. STUDY DESIGN: Population-based study. METHODS: Two Norwegian subpopulations with 2.6 million and 1.1 million inhabitants were investigated for the juvenile and adult forms of RRP, respectively, between the years of 1987 and 2009. Patients treated for RRP were identified in all ear/nose/throat departments located in the two areas. RESULTS: The overall incidence rates of RRP in juveniles and adults were 0.17 (95% confidence interval [CI], 0.10-0.25) and 0.54 (95% CI, 0.44-0.65) per 100,000, respectively. We found a preponderance of males in both groups (P = .000 for adults and P = .038 for children). There was no significant change in the yearly incidence rate during the study period, for either adults or children, even when stratifying for gender in each group. The median age at onset was 4 years for children and 34 years for adults, with no significant difference between genders, nor significant changes during the study years. CONCLUSIONS: This study does not support our hypothesis of an increasing incidence of RRP, for either children or adults. The estimated incidence rates in the Norwegian subpopulations are consistent with former population-based studies. Male preponderance in children was an unexpected finding. Further studies are warranted.

Failure to increase insulin secretory capacity during pregnancy-induced insulin resistance is associated with ethnicity and gestational diabetes.

OBJECTIVE: To assess changes in insulin resistance and ß-cell function in a multiethnic cohort of women in Oslo, Norway, from early to 28 weeks' gestation and 3 months post partum and relate the findings to gestational diabetes mellitus (GDM). METHOD: Population-based cohort study of 695 healthy pregnant women from Western Europe (41%), South Asia (25%), Middle East (15%), East Asia (6%) and elsewhere (13%). Blood samples and demographics were recorded at mean 15 (V1) and 28 (V2) weeks' gestation and 3 months post partum (V3). Universal screening was by 75 g oral glucose tolerance test at V2, GDM with modified IADPSG criteria (no 1-h measurement): fasting plasma glucose (PG) ≥5.1 or 2-h PG ≥8.5 mmol/l. Homeostatic model assessment (HOMA)-ß (ß-cell function) and HOMA-IR (insulin resistance) were calculated from fasting glucose and C-peptide. RESULT: Characteristics were comparable across ethnic groups, except age (South Asians: younger, P<0.001) and prepregnant BMI (East Asians: lower, P=0.040). East and South Asians were more insulin resistant than Western Europeans at V1. From V1 to V2, the increase in insulin resistance was similar across the ethnic groups, but the increase in ß-cell function was significantly lower for the East and South Asians compared with Western Europeans. GDM women compared with non-GDM women were more insulin resistant at V1; from V1 to V2, their ß-cell function increased significantly less and the percentage increase in ß-cell function did not match the change in insulin resistance. CONCLUSION: Pregnant women from East Asia and South Asia were more insulin resistant and showed poorer HOMA-ß-cell function than Western Europeans.

Impact of ethnicity on gestational diabetes identified with the WHO and the modified International Association of Diabetes and Pregnancy Study Groups criteria: a population-based cohort study.

OBJECTIVE: The International Association of Diabetes and Pregnancy Study Groups (IADPSG) recently proposed new criteria for diagnosing gestational diabetes mellitus (GDM). We compared prevalence rates, risk factors, and the effect of ethnicity using the World Health Organization (WHO) and modified IADPSG criteria. METHODS: This was a population-based cohort study of 823 (74% of eligible) healthy pregnant women, of whom 59% were from ethnic minorities. Universal screening was performed at 28±2 weeks of gestation with the 75 g oral glucose tolerance test (OGTT). Venous plasma glucose (PG) was measured on site. GDM was diagnosed as per the definition of WHO criteria as fasting PG (FPG) ≥7.0 or 2-h PG ≥7.8 mmol/l; and as per the modified IADPSG criteria as FPG ≥5.1 or 2-h PG ≥8.5 mmol/l. RESULTS: OGTT was performed in 759 women. Crude GDM prevalence was 13.0% with WHO (Western Europeans 11%, ethnic minorities 15%, P=0.14) and 31.5% with modified IADPSG criteria (Western Europeans 24%, ethnic minorities 37%, P< 0.001). Using the WHO criteria, ethnic minority origin was an independent predictor (South Asians, odds ratio (OR) 2.24 (95% confidence interval (CI) 1.26-3.97); Middle Easterners, OR 2.13 (1.12-4.08)) after adjustments for age, parity, and prepregnant body mass index (BMI). This increased OR was unapparent after further adjustments for body height (proxy for early life socioeconomic status), education and family history of diabetes. Using the modified IADPSG criteria, prepregnant BMI (1.09 (1.05-1.13)) and ethnic minority origin (South Asians, 2.54 (1.56-4.13)) were independent predictors, while education, body height and family history had little impact. CONCLUSION: GDM prevalence was overall 2.4-times higher with the modified IADPSG criteria compared with the WHO criteria. The new criteria identified many subjects with a relatively mild increase in FPG, strongly associated with South Asian origin and prepregnant overweight.

Pentraxin-3 in chronic heart failure: the CORONA and GISSI-HF trials.

AIMS: Pentraxin-3 (PTX3) is a component of the humoral arm of innate immunity which can regulate inflammatory processes. Since the role of inflammation in the progression of chronic heart failure (HF) is debated, we investigated the prognostic value of PTX3 and the effect of a statin in two large populations of patients with HF. METHODS AND RESULTS: Plasma levels of PTX3 were measured at randomization and after 3 months in 1457 patients enrolled in the Controlled Rosuvastatin Multinational Trial in HF (CORONA) and 1233 patients enrolled in the GISSI-Heart Failure trial (GISSI-HF). The relationships between baseline PTX3 levels or their changes over time and mortality were evaluated with multivariable Cox proportional hazard models including clinical factors, high sensitivity C-reactive protein (hsCRP), and N-terminal pro brain natriuretic peptide (NT-proBNP). PTX3 concentration [median (Q1-Q3) = 5.34 (3.55-7.64) ng/mL, n = 2690] was higher in females, in older patients, and those with lower body mass index. Baseline elevated PTX3 was associated with a higher risk of all-cause mortality [759 events, hazard ratio (HR) for 1 SD increase 1.20, 95% confidence interval (CI) 1.12-1.30, P < 0.0001], cardiovascular mortality (587 events, HR 1.27, 95% CI 1.17-1.38, P < 0.0001), or hospitalization for worsening HF (720 events, HR 1.21, 95% CI 1.12-1.30, P < 0.0001), and marginally improved discrimination. Three-month changes in PTX3 were associated with fatal events after adjustment for hsCRP or NT-proBNP. Rosuvastatin lowered hsCRP levels but significantly raised PTX3. CONCLUSION: In two independent clinical trials that enrolled patients with chronic HF, PTX3 was consistently associated with outcomes. The opposite effects of a statin on hsCRP and PTX3 call for further investigation. TRIAL REGISTRATION: NCT00336336 (GISSI-HF), NCT00206310 (CORONA).